Arixtra

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hemorrhage

Use ARIXTRA with extreme caution in conditions with
increased risk of hemorrhage, such as congenital or acquired bleeding
disorders, active ulcerative and angiodysplastic gastrointestinal disease,
hemorrhagicstroke, uncontrolled arterial hypertension, diabetic retinopathy,
or shortly after brain, spinal, or ophthalmological surgery. Isolated cases of
elevated aPTT temporally associated with bleeding events have been reported
following administration of ARIXTRA (with or without concomitant administration
of other anticoagulants) [See ADVERSE REACTIONS].

Do not administer agents that enhance the risk of
hemorrhage with ARIXTRA unless essential for the management of the underlying
condition, such as vitamin K antagonists for the treatment of VTE. If
co-administration is essential, closely monitor patients for signs and symptoms
of bleeding.

Do not administer the initial dose of ARIXTRA earlier
than 6 to 8 hours after surgery. Administration earlier than 6 hours after
surgery increases risk of major bleeding [see DOSAGE AND ADMINISTRATION and
ADVERSE REACTIONS].

Renal Impairment And Bleeding Risk

ARIXTRA increases the risk of bleeding in patients with
impaired renal function due to reduced clearance [seeCLINICAL PHARMACOLOGY].

The incidence of major bleeding by renal function status
reported in clinical trials of patients receiving ARIXTRA for VTE surgical
prophylaxis is provided in Table 1. In these patient populations, the following
is recommended:

Do not use ARIXTRA for VTE prophylaxis and treatment in
patients with CrCl < 30 mL/min [see CONTRAINDICATIONS].

Use ARIXTRA with caution in patients with CrCl 30 to 50
mL/min.

Table 1: Incidence of Major Bleeding in Patients
Treated With ARIXTRA by Renal Function Status for Surgical Prophylaxis and
Treatment of Deep Vein Thrombosis (DVT)

Assess renal function periodically in patients receiving
ARIXTRA. Discontinue the drug immediately in patients who develop severe renal
impairment while on therapy. After discontinuation of ARIXTRA, its
anticoagulant effects may persist for 2 to 4 days in patients with normal renal
function (i.e., at least 3 to 5 half-lives). The anticoagulant effects of ARIXTRA
may persist even longer in patients with renal impairment [seeCLINICAL
PHARMACOLOGY].

Body Weight < 50 Kg And Bleeding Risk

ARIXTRA increases the risk for bleeding in patients who
weigh less than 50 kg, compared to patients with higher weights.

During the randomized clinical trials of VTE prophylaxis
in the peri-operative period following hip fracture, hip replacement, or knee
replacement surgery and abdominal surgery, major bleeding occurred at a higher
rate among patients with a body weight < 50 kg compared to those with a body
weight > 50 kg (5.4% versus 2.1% in patients undergoing hip fracture, hip replacement,
or knee replacement surgery; 5.3% versus 3.3% in patients undergoing abdominal surgery).

Thrombocytopenia

Thrombocytopenia can occur with the administration of
ARIXTRA. Thrombocytopenia of any degree should be monitored closely.
Discontinue ARIXTRA if the platelet count falls below 100,000/mm3. Moderate
thrombocytopenia (platelet counts between 100,000/mm3 and 50,000/mm3) occurred
at a rate of 3.0% in patients given ARIXTRA 2.5 mg in the peri-operative hip
fracture, hip replacement, or knee replacement surgery and abdominal surgery
clinical trials. Severe thrombocytopenia (platelet counts less than 50,000/mm )
occurred at a rate of 0.2% in patients given ARIXTRA 2.5 mg in these clinical
trials. During extended prophylaxis, no cases of moderate or severe
thrombocytopenia were reported.

Moderate thrombocytopenia occurred at a rate of 0.5% in
patients given the ARIXTRA treatment regimen in the DVT and PE treatment
clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in
patients given the ARIXTRA treatment regimen in the DVT and PE treatment
clinical trials.

Spinal or epidural hematomas, which may result in
long-term or permanent paralysis, can occur with the use of anticoagulants and
neuraxial (spinal/epidural) anesthesia or spinal puncture. The risk of these
events may be higher with post-operative use of indwelling epidural catheters
or concomitant use of other drugs affecting hemostasis such as NSAIDs [seeBOXED WARNING]. In the postmarketing experience, epidural or spinal
hematoma has been reported in association with the use of ARIXTRA by
subcutaneous (SC) injection. Monitor patients undergoing these procedures for
signs and symptoms of neurologic impairment. Consider the potential risks and
benefits before neuraxial intervention in patients anticoagulated or who may be
anticoagulated for thromboprophylaxis.

Monitoring: Laboratory Tests

Routine coagulation tests such as Prothrombin Time (PT)
and Activated Partial Thromboplastin Time (aPTT) are relatively insensitive
measures of the activity of ARIXTRA and international standards of heparin or
LMWH are not calibrators to measure anti-Factor Xa activity of ARIXTRA. If
unexpected changes in coagulation parameters or major bleeding occur during
therapy with ARIXTRA, discontinue ARIXTRA. In postmarketing experience,
isolated occurrences of aPTT elevations have been reported following
administration of ARIXTRA [see ADVERSE REACTIONS].

Periodic routine complete blood counts (including
platelet count), serum creatinine level, and stool occult blood tests are
recommended during the course of treatment with ARIXTRA. The anti-Factor Xa
activity of fondaparinux sodium can be measured by anti-Xa assay using the
appropriate calibrator (fondaparinux). The activity of fondaparinux sodium is expressed
in milligrams (mg) of the fondaparinux and cannot be compared with activities
of heparin or low molecular weight heparins. [See CLINICAL PHARMACOLOGY]

Patient Counseling Information

Patient Advice

If the patients have had neuraxial anesthesia or spinal
puncture, and particularly, if they are taking concomitant NSAIDS, platelet
inhibitors, or other anticoagulants, they should be informed to watch for signs
and symptoms of spinal or epidural hematomas, such as tingling, numbness
(especially in the lower limbs) and muscular weakness. If any of these symptoms
occur, the patients should contact his or her physician immediately.

The use of aspirin and other NSAIDS may enhance the risk
of hemorrhage. Their use should be discontinued prior to ARIXTRA therapy
whenever possible; if co-administration is essential, the patient's clinical
and laboratory status should be closely monitored. [See DRUG INTERACTIONS]

If patients must self-administer ARIXTRA (e.g., if
ARIXTRA is used at home), they should be advised of the following:

ARIXTRA should be given by subcutaneous injection.
Patients must be instructed in the proper technique for administration.

As with all anticoagulants, the most important risk with
ARIXTRA administration is bleeding. Patients should be counseled on signs and
symptoms of possible bleeding.

It may take them longer than usual to stop bleeding.

They may bruise and/or bleed more easily when they are
treated with ARIXTRA.

They should report any unusual bleeding, bruising, or
signs of thrombocytopenia (such as a rash of dark red spots under the skin) to
their physician [see WARNINGS AND PRECAUTIONS].

To tell their physicians and dentists they are taking
ARIXTRA and/or any other product known to affect bleeding before any surgery is
scheduled and before any new drug is taken [see WARNINGS AND PRECAUTIONS].

To tell their physicians and dentists of all medications
they are taking, including those obtained without a prescription, such as
aspirin or other NSAIDs. [See DRUG INTERACTIONS].

Keep out of the reach of children.

FDA-Approved Patient Labeling

Patient labeling is provided as a tear-off leaflet at the
end of this full prescribing information.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No long-term studies in animals have been performed to
evaluate the carcinogenic potential of fondaparinux sodium.

At subcutaneous doses up to 10 mg/kg/day (about 32 times
the recommended human dose based on body surface area), fondaparinux sodium was
found to have no effect on fertility and reproductive performance of male and
female rats.

Use In Specific Populations

Pregnancy

Pregnancy Category B

Reproduction studies have been performed in pregnant rats
at subcutaneous doses up to 10 mg/kg/day (about 32 times the recommended human
dose based on body surface area) and pregnant rabbits at subcutaneous doses up
to 10 mg/kg/day (about 65 times the recommended human dose based on body
surface area) and have revealed no evidence of impaired fertility or harm to
the fetus due to fondaparinux sodium. There are, however, no adequate and
well-controlled studies in pregnant women. Because animal reproduction studies
are not always predictive of human response, ARIXTRA should be used during
pregnancy only if clearly needed.

Nursing Mothers

Fondaparinux sodium was found to be excreted in the milk
of lactating rats. However, it is not known whether this drug is excreted in
human milk. Because many drugs are excreted in human milk, caution should be
exercised when ARIXTRA is administered to a nursing mother.

Pediatric Use

Safety and effectiveness of ARIXTRA in pediatric patients
have not been established. Because risk for bleeding during treatment with
ARIXTRA is increased in adults who weigh < 50 kg, bleeding may be a
particular safety concern for use of ARIXTRA in the pediatric population [see WARNINGS
AND PRECAUTIONS].

Geriatric Use

In clinical trials the efficacy of ARIXTRA in the elderly
(65 years or older) was similar to that seen in patients younger than 65 years;
however, serious adverse events increased with age. Exercise caution when using
ARIXTRA in elderly patients, paying particular attention to dosing directions
and concomitant medications (especially anti-platelet medication). [See WARNINGS
AND PRECAUTIONS]

Fondaparinux sodium is substantially excreted by the
kidney, and the risk of adverse reactions to ARIXTRA may be greater in patients
with impaired renal function. Because elderly patients are more likely to have
decreased renal function, assess renal function prior to ARIXTRA
administration. [See CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS,
and CLINICAL PHARMACOLOGY]

In the peri-operative hip fracture, hip replacement, or
knee replacement surgery clinical trials with patients receiving ARIXTRA 2.5
mg, serious adverse events increased with age for patients receiving ARIXTRA.
The incidence of major bleeding in clinical trials of ARIXTRA by age is
provided in Table 6.

Table 6: Incidence of Major Bleeding in Patients
Treated With ARIXTRA by Age

Renal Impairment

Patients with impaired renal function are at increased
risk of bleeding due to reduced clearance of ARIXTRA [see CONTRAINDICATIONS
and WARNINGS AND PRECAUTIONS]. Assess renal function periodically in
patients receiving ARIXTRA. Discontinue ARIXTRA immediately in patients who
develop severe renal impairment while on therapy. After discontinuation of ARIXTRA,
its anticoagulant effects may persist for 2 to 4 days in patients with normal
renal function (i.e., at least 3 to 5 half-lives). The anticoagulant effects of
ARIXTRA may persist even longer in patients with renal impairment [see CLINICAL
PHARMACOLOGY].

Hepatic Impairment

Following a single, subcutaneous dose of 7.5 mg of
ARIXTRA in patients with moderate hepatic impairment (Child-Pugh Category B)
compared to subjects with normal liver function, changes from baseline in aPTT,
PT/INR, and antithrombin III were similar in the two groups. However, a higher
incidence of hemorrhage was observed in subjects with moderate hepatic impairment
than in normal subjects, especially mild hematomas at the blood sampling or injection
site. The pharmacokinetics of fondaparinux have not been studied in patients
with severe hepatic impairment. [See DOSAGE AND ADMINISTRATION and CLINICAL
PHARMACOLOGY.]

Last reviewed on RxList: 7/29/2014
This monograph has been modified to include the generic and brand name in many instances.